A Prospective Survey of Skin Manifestations in Children With Inborn Errors of Immunity From a National Registry Over 17 Years

Abstract

Background and ObjectivesReports on skin manifestations in inborn errors of immunity (IEI) are based on retrospective analysis, small series, or isolated case reports. The present prospective study aimed to determine the spectrum of skin manifestations in children with IEI and their relevance to specific molecular defects.Materials and MethodsThe data were obtained from the Kuwait National Primary Immunodeficiency Disorders Registry during the period of 2004–2020.ResultsA total of 313 pediatric cases of IEI, 71% diagnosed at molecular level, were registered with a cumulative follow-up period of 29,734 months. Skin manifestations were seen in 40.3% of the patients, and they were among the presenting manifestations in 33%. Patients with skin manifestations were older at both onset and diagnosis ages of IEI symptoms, but this was statistically significant for the latter only. The diagnosis delay was significantly longer in patients with skin manifestations. There was a statistically significant association between having skin manifestations and IEI category, being more common in patients with complement deficiencies, combined immunodeficiencies, and diseases of immune dysregulation. There was no statistically significant association between having skin manifestations and both gender and survival. Skin infections were the most frequent manifestations followed by eczema and autoimmune associations. Among IEI with more than 10 cases, skin lesions were a consistent finding in dedicator of cytokinesis 8 (DOCK8) deficiency, hyper IgE syndrome, ataxia-telangiectasia, and recombination activation gene (RAG)1 deficiency.ConclusionsSkin manifestations are common in IEI patients, and they had significant diagnosis delay and referral to specialists. Improvement of awareness about IEI is needed among pediatricians and dermatologists.

Inmunodeficiencia combinada debida a deficiencia de DOCK8. Lo que sabemos hasta ahora

“…25 En edades tempranas, los pacientes presentan eccema agudo diseminado con eritema y aspecto húmedo, que no remite fácilmente, por lo que progresa al llamado eccema crónico con liquenificación o variedades graves infrecuentes tipo prurigo nodular (Figuras 5A, 5B y 5C). 26,27,28,29 Figura 2. Consecuencias de la deficiencia de DOCK8 en las células inmunitarias.…”

“…La participación de IL-31 en la patogénesis del prurito en pacientes con Def-DOCK8 abre una ventana de oportunidad para terapias blanco-dirigidas en este grupo de pacientes. 28,29,30 La proteína DOCK8 es necesaria para la adecuada organización citoesquelética de los linfocitos; la disfunción citoesquelética en los linfocitos T CD8+ y NK les impide migrar y poblar tejidos con una estructura densa de colágeno, como la piel, resultando en la muerte de los linfocitos por citotripsis y la ausencia de linfocitos T CD8+ de memoria residentes. Este fenómeno, citotripsis, se refiere a la muerte celular por pérdida estructural, con deformidad nuclear y alargamiento de las células inmunitarias cuando migran a través de tejidos densos como la piel; se observa también en células dendríticas de pacientes con Def-DOCK8 y se ha propuesto como un estudio diagnóstico confirmatorio.…”

“…Este fenómeno, citotripsis, se refiere a la muerte celular por pérdida estructural, con deformidad nuclear y alargamiento de las células inmunitarias cuando migran a través de tejidos densos como la piel; se observa también en células dendríticas de pacientes con Def-DOCK8 y se ha propuesto como un estudio diagnóstico confirmatorio. 28,29,31 El defecto de barrera cutánea aunado a los defectos funcionales en los linfocitos T, B y NK incrementa el riesgo de infecciones virales, especialmente por la familia herpesviridae y virus de papiloma humano (VPH), lo que incrementa el riesgo de neoplasias epiteliales (véase la sección Cáncer). 28,32,33 Los biomarcadores de linfocitos son una herramienta potencial para cribaje y diagnóstico diferencial de la Def-DOCK8 en los pacientes con eccema grave (Figura 5D), y para determinar si es necesario realizar pruebas diagnósticas más exhaustivas.…”

Atopic Dermatitis-like Genodermatosis: Disease Diagnosis and Management

“…Primary immunodeficiency diseases (PIDDs) is a group of mostly monogenic disorders with immune system dysfunction, characteristically presenting with recurrent infections [ 3 ]. As for skin manifestations, atopic dermatitis-like lesion is a common finding among several PIDDs, being reported in 13% to 57% of patients with PIDDs in previous studies [ 4 , 5 , 6 , 7 ]. In particular, the skin lesion might be the early or heralding manifestation of some immunodeficiency diseases, emphasizing the importance to distinguish it from atopic dermatitis and detect the underlying life-threatening immunologic defects [ 4 ].…”

“…As for skin manifestations, atopic dermatitis-like lesion is a common finding among several PIDDs, being reported in 13% to 57% of patients with PIDDs in previous studies [ 4 , 5 , 6 , 7 ]. In particular, the skin lesion might be the early or heralding manifestation of some immunodeficiency diseases, emphasizing the importance to distinguish it from atopic dermatitis and detect the underlying life-threatening immunologic defects [ 4 ]. Here, we focus on the PIDDs commonly presented with atopic dermatitis-like skin lesions, including hyper-immunoglobulin E (IgE) syndromes (HIES), Wiskott-Aldrich syndrome (WAS), immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, STAT5B deficiency, Omenn syndrome (OS), atypical complete DiGeorge syndrome, and X-linked agammaglobulinemia (XLA).…”